Accelerated atherosclerosis in ApoE deficient lupus mouse models.

Area of Science:

• Immunology
• Cardiovascular Research
• Genetics

Background:

• Accelerated atherosclerosis and cardiovascular disease risk in systemic lupus erythematosus (SLE) patients lack clear mechanistic understanding.
• Development of appropriate mouse models is crucial for elucidating the link between SLE and atherosclerosis.

Purpose of the Study:

• To investigate the interplay between atherosclerosis and SLE using combined murine models.
• To understand the mechanisms underlying accelerated atherosclerosis in SLE patients.

Main Methods:

• Crossed the ApoE(-/-) atherosclerosis model with three distinct murine SLE models (cGVH induction, Fas deficiency, MRL/lpr background).
• Analyzed atherosclerosis development, B cell phenotypes (MHC II, Fas, CD86, marginal zone markers), and autoantibody titers (anti-oxLDL, anti-cardiolipin, anti-dsDNA, anti-chromatin).

Main Results:

• All combined models showed a modest increase in atherosclerosis compared to controls.
• B cells in ApoE(-/-) mice exhibited distinct phenotypes, including higher MHC II, Fas, CD86 expression, and increased marginal zone cells.
• Induction of cGVH led to marginal zone B cell depletion, increased autoantibodies (anti-oxLDL, anti-cardiolipin, anti-dsDNA, anti-chromatin), and exacerbated atherosclerosis.

Conclusions:

• Murine models combining SLE induction with ApoE deficiency demonstrate a connection between lupus-like symptoms and accelerated atherosclerosis.
• B cell alterations and autoantibody production are implicated in the exacerbation of atherosclerosis in these models.
• Fas deficiency and cGVH induction can worsen atherosclerosis in ApoE-deficient mice.